Distributed Diffusion–Clearance Model for Transient Drug Distribution within the Skin

Kretsos, Kosmas; Kasting, Gerald B.; Nitsche, Johannes C. C.

doi:10.1002/jps.20187

Cited by 50 publications

(22 citation statements)

References 47 publications

(68 reference statements)

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“…It was concluded that the previously published in vivo human experimental data are not consistent with the assumption of transport in the dermis due to molecular diffusion only, and the dispersion coefficient, which is about an order of magnitude larger, has to be used instead. Our analysis suggests that transport occurs mostly by blood/lymphatic flow rather than molecular diffusion explaining the transport of solutes to deeper tissues, as assumed previously (8)(9)(10).…”

Section: Discussionmentioning

confidence: 78%

“…This will only be true if D t is large enough. In previous studies (8)(9)(10), it was assumed that the transport in the dermis is solely due to solute diffusion (D t =D). To test this assumption we substituted D t =D in Eq.…”

Section: Resultsmentioning

confidence: 99%

“…Others have previously assumed that only molecular diffusion in the dermis has contributed to penetration to deeper layers of dermis, and therefore used the simplified model (as defined in Eq. 1) to model tissue concentration-distance profiles (8)(9)(10). In general, molecular diffusion was assumed a priori, in order to enable modelling in the steady state.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Modelling Dermal Drug Distribution After Topical Application in Human

Anissimov

Roberts

2011

Pharm Res

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Section: Discussionmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Modelling Dermal Drug Distribution After Topical Application in Human

Anissimov

Roberts

2011

Pharm Res

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“…The microenvironment inside the skin is a vibrant part of the body which alters constantly (Krestos, Kasting, 2005). The skin possesses a rich vascular network system which regulates and deals various activities in the skin (Krestos et al, 2004). Cutaneous microvasculature is enclosed in the papillary dermis (1-2 mm below the epidermal surface) and consists of two horizontal plexus (Haake, Holbrook, 1999;Cevc, Vierl, 2007).…”

Section: Skin Drug Clearancementioning

confidence: 99%

Basic considerations in the dermatokinetics of topical formulations

Nair

Jacob

Al‐Dhubiab

et al. 2013

Braz. J. Pharm. Sci.

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Assessing the bioavailability of drug molecules at the site of action provides better insight into the efficiency of a dosage form. However, determining drug concentration in the skin layers following topical application of dermatological formulations is a great challenge. The protocols followed in oral formulations could not be applied for topical dosage forms. The regulatory agencies are considering several possible approaches such as tape stripping, microdialysis etc. On the other hand, the skin bioavailability assessment of xenobiotics is equally important for topical formulations in order to evaluate the toxicity. It is always possible that drug molecules applied on the skin surface may transport thorough the skin and reaches systemic circulation. Thus the real time measurement of molecules in the skin layer has become obligatory. In the last two decades, quite a few investigations have been carried out to assess the skin bioavailability and toxicity of topical/dermatological products. This review provides current understanding on the basics of dermatokinetics, drug depot formation, skin metabolism and clearance of drug molecules from the skin layers following application of topical formulations.Uniterms: Dermatological formulations/pharmacokinetics. Dermatological formulations/ toxicity. Dermatokinetics. Skin/metabolism. Microdialysis. Tape stripping.A avaliação da biodisponibilidade de moléculas de fármacos no sítio de ação oferece melhor compreensão sobre a eficiência da forma de dosagem. Entretanto, a determinação da concentração de fármaco nas camadas da pele em seguida à aplicação tópica de formulações dermatológicas é um grande desafio. Os protocolos seguidos para as formulações orais não podem ser aplicados para as formulações tópicas. As agências regulatórias consideram várias abordagens possíveis, tape stripping, microdiálise etc. Por outro lado, a avaliação da biodisponibilidade de xenobióticos na pele é igualmente importante para as formulações tópicas para se avaliar a toxicidade. É sempre possível que as moléculas de fármaco aplicadas na superfície da pele sejam transportadas através da pele e alcancem a circulação sistêmica. Assim, a medida em tempo real de moléculas na camada da pele tem se tornado obrigatória. Nas últimas duas décadas, realizaram-se poucas pesquisas para avaliar a biodisponibilidade da pele e a toxicidade de produtos tópicos/dermatológicos. Esta revisão fornece a compreensão atual com base na dermatocinética, formação de fármaco de depósito, metabolismo da pele e o clearance das moléculas de fármaco das camadas da pele em seguida à aplicação de formulações tópicas.Unitermos: Formulações dermatológicas/farmacocinética. Formulações dermatológicas/toxicidade. Dermatocinética Pele/metabolismo. Microdiálise. Tape stripping.

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“…Kretsos et al reanalyzed the data and confirmed the consistency with their own similar distributed diffusion-clearance model. [21] Following the previous research, Kretsos and Kasting created a new model to explain the dermal capillary clearance process based on assumed periodic microscopic distribution of dermal capillaries in three-dimensional space. The downfall of this model is that it only applies to the steady-state scenario and explains localized concentration in dermis.…”

Section: New Physiological Modelsmentioning

confidence: 99%

Deep Percutaneous Penetration into Muscles and Joints: Update

Doktor

Lee

Maibach³

2014

Topical Drug Bioavailability, Bioequivalence, and Penetration

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A b s t r a c tTransdermal drug delivery is a multifactorial process with variable penetration mechanisms. Adverse effects associated with nonsteroidal anti-inflammatory drugsÊ (NSAIDs) use in treatment for joint and muscle diseases are sufficiently severe to consider topical application. A drug's lipophilicity, fraction unbound and permeability found in the viable skin are some of the physiochemical factors influencing the delivery mechanism of transdermal absorption. These and other variables play a role in determining if the drug reaches the deep tissues via direct penetration from dermal or systemic blood redistribution. Pharmacokinetic models have been developed to help elucidate penetration routes and efficacy for various drugs. Improvements in modes of transdermal delivery through active research projects including relevant animal models and human translational research may introduce advances in clinical development of treatments.

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Distributed Diffusion–Clearance Model for Transient Drug Distribution within the Skin

Cited by 50 publications

References 47 publications

Modelling Dermal Drug Distribution After Topical Application in Human

Modelling Dermal Drug Distribution After Topical Application in Human

Basic considerations in the dermatokinetics of topical formulations

Deep Percutaneous Penetration into Muscles and Joints: Update

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